The specific aims of the Laboratory Cancer Research Center at the Eppley Institute for Research in Cancer and Allied Diseases are to carry out interdisciplinary research in: 1) cancer cause and prevention aimed at determining the mechanisms of action of chemical carcinogens, including the mechanisms of activation of carcinogens and their interactions with DNA, the role of potential environmental carcinogens in human cancer, the interaction of oncogenes and chemical carcinogens in tumor initiation and promotion, and the role of dietary factors in causing and preventing cancer; 2) molecular and cellular biology , including DNA replication, mechanisms of gene transcription, the mechanisms of action of growth factors and hormones, characterization of growth factor receptors and their signal transduction mechanisms, the role of oncogene expression in cellular differentiation, mechanisms of viral reproduction and oncogene activation, and DNA-protein interactions; and 3) developmental therapeutics, including characterization of tumor markers, isolation and characterization of tumor-associated antigens, development of monoclonal antibodies, development of antisense and triple helical-forming oligonucleotides to inhibit cancer cell growth, synthesis of novel antineoplastic agents, use of peripheral stem cells and cytokines in bone marrow transplantation, and design of protocols for improved drug delivery and pharmacokinetic analysis of anticancer agents. To achieve these specific aims we have assembled a group of 52 faculty with expertise in chemistry, biochemistry, cell biology, molecular biology, immunology, pathology, virology, pharmacology, toxicology, nutrition, and clinical oncology. In support of this research we have established core laboratory facilities in animal care, cell culture, histology, molecular biology including 2-dimensional gel electrophoresis, mass spectrometry, nuclear magnetic resonance spectrometry, computer services including molecular modeling and DNA and protein data base analysis, drug analysis and pharmacokinetics, microbial mutagenesis, glassware washing, and safety. In addition, we have established a Leukemia/Lymphoma Tissue Procurement Service that supports a region-wide program for data collection and protocol standardization. The Core Grant faculty also comprise the nucleus of our Cancer Biology Training Program for the education and research training of predoctoral and postdoctoral students.